p53 is involved in numerous cellular processes, but is most well-known for its roles in the DNA damage response and in tumor suppression. Extracellular stresses such as chemotherapy and ionizing radiation can damage genomic DNA, which is detected by ATR and ATM, protein kinases that phosphorylate p53. Alternatively, UV damage signals through JNK and p38 MAP kinases to induce p53 activation. Once activated, p53 promotes inhibition of angiogenesis and turns on gene expression for DNA repair. Depending on the level of cellular damage, p53 can induce caspase activation and cell death through the intrinsic or extrinsic apoptosis pathways. p53 is negatively regulated by ubiquitin ligase MDM2, which targets p53 for proteasomal degradation.
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